BiochemProbe — Life Science Research Reagents

NVP-LDE225 free base · Synonyms: Erismodegib | LDE225 | NVP-LDE225

Sonidegib is a potent and selective Smo antagonist.

For research use only. Not for human or veterinary use.

Target Smo
Research area Cancer
Purity >98% Stock Inquire
Data Sheet SDS COA

NVP-LDE225 structure

CAS No.: 956697-53-3

Download structure (.mol)

Pack sizes & pricing

Size Price SKU Stock
1 g USD 240.00 BP-02471-1g In stock Get quote
2 g USD 380.00 BP-02471-2g In stock Get quote
3 g USD 460.00 BP-02471-3g In stock Get quote
5 g USD 614.00 BP-02471-5g In stock Get quote
10 g USD 980.00 BP-02471-10g In stock Get quote

Need another size or custom synthesis? Request a quote.

Description

Sonidegib (Erismodegib) is a potent and selective Smo antagonist with IC50 of 1.3 nM and 2.5 nM for mouse and human Smo in binding assay, respectively .

Biological activity

In Vitro The IC50 values for Sonidegib (NVP-LDE225) for the major human CYP450 drug metabolizing enzymes is greater than 10 μM[1]. Sonidegib (LDE225), a small molecule, clinically investigated SMO inhibitor, used alone and in combination with Nilotinib, inhibits the Hh pathway in CD34+ chronic phase (CP)-chronic myeloid leukaemia (CML) cells, reducing the number and self-renewal capacity of CML leukaemia stem cell (LSC). Sonidegib interacts directly with SMO, in a similar fashion to cyclopamine, to reduce expression of downstream Hh signaling targets. Primary CD34+ CP-CML cells are cultured in serum free media (SFM)±Sonidegib for 6, 24 and 72 hours (h). At 72 h, while there is variability between the biological samples, GLI1 is significantly downregulated following exposure to Sonidegib (10 nM; 0.78-fold and 100 nM; 0.73-fold, respectively (p<0.01). In Vivo Sonidegib (NVP-LDE225) is a weak base with a measured pKa of 4.2 and exhibits relatively poor aqueous solubility. In the subcutaneous Ptch+/-p53-/- medulloblastoma allograft mouse model, Sonidegib demonstrates dose-related antitumor activity after 10 days of oral administration of a suspension of the diphosphate salt. At a dose of 5 mg/kg/day qd, Sonidegib significantly inhibits tumor growth, corresponding to a T/C value of 33% (p<0.05 as compared to vehicle controls). When dosed at 10 and 20 mg/kg/day qd, Sonidegib affords 51 and 83% regression, respectively[1]. Bone marrow cells and spleen cells from a subset of treated mice are transplanted into secondary recipient mice. Transplantation of either bone marrow (BM) or spleen cells from mice treated with Sonidegib (LDE225)+Nilotinib results in reduced white cell count (WCC) and reduces leukaemia development in secondary recipients compared to Sonidegib or Nilotinib alone.

Identifiers

SMILES
C[C@H]1CN(C[C@@H](C)O1)C1=CC=C(NC(=O)C2=C(C)C(=CC=C2)C2=CC=C(OC(F)(F)F)C=C2)C=N1
InChIKey
VZZJRYRQSPEMTK-CALCHBBNSA-N

Specifications

MW (average)
485.4981
Formula
C26H26F3N3O3
CAS No.
956697-53-3
Physical state
Solid
Color
White to light yellow
Shipping
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage
Powder -20°C, 3 years , 4°C, 2 years ; In solvent -20°C, 1 year;

Solubility

Soluble in DMSO

Documents

References

[1].Pan S, et al. Discovery of NVP-LDE225, a Potent and Selective Smoothened Antagonist. ACS Med Chem Lett. 2010 Mar 16;1(3):130-4.
[2]. Irvine DA, et al. Deregulated hedgehog pathway signaling is inhibited by the smoothened antagonist LDE225 (Sonidegib) in chronic phase chronic myeloid leukaemia. Sci Rep. 2016 May 9;6:25476.

Same target

Search Smo

Same research area

Search Cancer